Interesting question
I had to think about that for a bit. There is a good chance that it might become an article. But for now, if you are using Microsoft products, I would suggest making absolutely sure that the computer is up-to-date with regards to the operating system and every application.
Next you need to get a good idea of what should be running on your computer. I would suggest using System Information for that. Start/Programs/Accessories/System Tools/System Information. Pay special attention to Software Environment. Get familiar with what drivers, connections, running tasks, services and so on.
That way if some unusual process or service show up you will know it.
I am curious as to why you want to do this without any tools.
